The objectives of this project are two-fold: (a) An exploration of the function of vitamin A in maintenance of corneal epithelium: a specific, identifiable glycoprotein (GP) is released into the medium of cultured corneas within 3 hr. of incubation and stimulated several-fold by very low concentrations of added vitamin A. The mechanism of this stimulation (transcriptional vs. post-translational, i.e. on sugar transfer in GP synthesis) will be explored, as well as the character of the stimulated GP, in order to approach the possibly primary function of vitamin A in corneal epithelium. The destination of the stimulated GP (basement membrane, stroma or secreted) will be studied by radioautography. (b) An investigation of the release of corneal collagenase in keratomalacia, and the mechanism of collagenase inhibition by serum alpha 1-macroglobulin (alpha 1-m) will be made. Slight thermal burns are used on corneas of mildly vitamin A-deficient rats to produce ulcers, and compared to ulcers formed in severely-burned normal corneas. These ulcerating corneas release collagenase. The time-sequence and mechanism of this release; whether the collagenase in normal, burned corneas is "latent" and in the deficient-burned "manifest"; the complexing and inhibition of the collagenase with a1-m and characterization of the complexing, will be explored. Ultimately, we wish to determine wether "corneal melting" in keratomalacia is caused by lack of inhibition of collagenase as a result of insufficient serum a1-m in vitamin A deficiency.